title: miR-30e reciprocally regulates the differentiation of adipocytes and osteoblasts by directly targeting low-density lipoprotein receptor-related protein 6.
abstract: Reciprocal relationship usually exists between osteoblastogenesis and adipogenesis, with factors stimulating one of these processes at the same time inhibiting the other. In the present study, miR-30e was found to be involved in the reciprocal regulation of osteoblast and adipocyte differentiation. Our data indicated that miR-30e was induced in primarily cultured mouse bone marrow stromal cell, mesenchymal cell line C3H10T1/2 and preadipocyte 3T3-L1 after adipogenic treatment. Conversely, it was reduced in mouse stromal line ST2 and preosteoblast MC3T3-E1 after osteogenic treatment. Enforced expression of miR-30e in 3T3-L1 significantly suppressed the growth of the cells and induced the preadipocytes to differentiate into mature adipocytes, along with increased expression of adipocyte-specific transcription factors peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein-α (C/EBPα) and C/EBPβ, and the marker gene aP2. In contrast, inhibition of the endogenous miR-30e enhanced the cell growth and repressed preadipocytes to differentiate. Conversely, supplementing miR-30e activity blocked, whereas knocking down miR-30e enforced the preosteoblast MC3T3-E1 to fully differentiate. Furthermore, miR-30e overexpression stimulated adipocyte formation and inhibited osteoblast differentiation from marrow stromal cells. Low-density lipoprotein receptor-related protein 6 (LRP6), one of the critical coreceptor for Wnts, was shown to be a direct target of miR-30e by using the luciferase assay. Knockdown of LRP6 in 3T3-L1 cells downregulated β-catenin/T-cell factor (TCF) transcriptional activity and dramatically potentiated the differentiation of the cells into mature adipocytes. Taken together, the present work suggests that the expression of miR-30e is indispensable for maintaining the balance of adipocytes and osteoblasts by targeting the canonical Wnt/β-catenin signaling.
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Guan
authors.forename: F
authors.initials: F
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: Zhou
authors.forename: A
authors.initials: A
authors.lastname: Chang
authors.forename: B
authors.initials: B
authors.lastname: Sun
authors.forename: Y
authors.initials: Y
authors.lastname: Cai
authors.forename: Z
authors.initials: Z
authors.lastname: Ma
authors.forename: C
authors.initials: C
authors.lastname: Dai
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: B
authors.initials: B
authors.lastname: Wang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016086:Lentivirus / Q000378:metabolism; D060488:Low Density Lipoprotein Receptor-Related Protein-6 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D060488:Low Density Lipoprotein Receptor-Related Protein-6; D035683:MicroRNAs; C534715:Mirn30d microRNA, mouse